Description: (Applicant's Description) The Molecular and Structural Biology Program brings together 23 outstanding investigators representing 10 departments, 3 UCHSC Schools (Medicine, Pharmacy, and the Graduate school), and 2 sister institutions (UCHSC & CU-Boulder). The scientific and programmatic goals of the Program are to elucidate key fundamental processes involved in cancer biology and to expand the molecular structure component of the Program, respectively. Our tremendous success in developing a Structural Biology initiative has broadened our Program into cutting-edge areas of basic science. The Program has been re-organized and members are now divided into three focal points of strength: Nucleic Acid Metabolism, Gene Transcription and Molecular Structure. This very well funded group of investigators ($6.3 million; direct costs) has provided key insights into molecular mechanisms regulating: DNA replication, repair, and re-arrangements; RNA trans-splicing and mRNA processing; stage-, cell- and signal-specific gene transcription; and in elucidating the chemical structures of DNA, RNA, protein and drug molecules. During the past five years our Program has had dramatic increases in total support (23%), NCI support (537%), and other Cancer Support (254%), showing remarkable progress. Additionally, members have published more than 200 reports in highly respected journals, underscoring the national prominence of Program faculty. Program members interact via several mechanisms, including monthly seminars, annual retreat, annual regional topical meetings, and annual mini-symposium. These formal mechanisms of interaction provide multiple opportunities for exchange of information and collaborative efforts. The Program makes heavy use of the DNA Sequencing, Tissue Culture/Monoclonal Antibody, Protein Chemistry and Flow Cytometry Cores. Our future plans are to further develop the Molecular Structure group, particularly in the area of proteomics, and to provide critical insights into the molecular mechanisms by which aberrations of the DNA replication machinery, transcription apparatus, and RNA processing components lead to cancer.